In general, enzymes not only have high catalytic activity but also exhibit stereospecificity, substrate specificity and reaction specificity. The stereospecificity of an enzyme is almost absolute with some exceptions.
According to recent research, the importance of the use of optically active substances in the field of pharmaceuticals, pesticides, animal foods, spices, etc. is increasing. Specifically, optical isomers sometimes have completely different physiological activities to each other, and thus techniques to specifically obtain optical isomers are important. For example, when only one of two enantiomers has the physiological activity of interest, the problem of a mixture of the enantiomers is not only that the other isomer has no activity in the mixture but also may competitively inhibit the coexisting effective enantiomer. Because of such competition, the biological activity of a racemate may be greatly decreased up to ½ as compared with that of the effective enantiomer. Therefore, it is an industrially important objective to develop methods for obtaining optically pure enantiomers (synthesis or resolution).
A technique widely used to achieve the objective comprises the synthesis of racemate followed by effective optical resolution of the synthesized racemate. However, according to this technique comprising the optical resolution after synthesis, an unintended enantiomer is always synthesized as a by-product. Thus, this technique is still problematic with respect to efficient utilization of raw materials. Even when the recovered by-product is regenerated as the raw material, a constant amount of by-product is always repeatedly synthesized. Hence, an enzymatic optical resolution method that neither produces a by-product nor produces a large volume of waste liquid has been attracting attention. The enzymatic optical resolution method utilizes specific generation of an objective enantiomer by taking advantage of the specificity of enzymes. This method suppresses the synthesis of unnecessary enantiomer so that they are produced at low levels. As a result of this method, products with high optical purity can be readily obtained. In addition, this method is advantageous for its efficient use of raw materials.
Optically active α-hydroxy acids include optically active mandelic acid, which is useful as an intermediate for synthesizing pharmaceuticals and pesticides. Known methods for producing optically active mandelic acid having a substituent on the benzene ring include the following:                optical resolution method comprising fractional crystallization of racemates (Unexamined Published Japanese Patent Application No. (JP-A) 2001-72644);        chromatographic optical resolution (Journal of Chromatography, 282, 83–8, (1983));        method using nitrilase (JP-A Hei 4-99496; JP-A Hei 6-237789);        method for obtaining an optical isomer by oxidizing one of the isomer in a racemate (JP-A Hei 6-165695); and        method using hydroxylnitrile lyase (JP-A 2001-354616).        
The method using nitrilase requires a mandelonitrile derivative as the raw material. Sodium cyanide is necessary for the synthesis of the mandelonitrile derivative.
On the other hand, the method using hydroxylnitrile lyase requires benzaldehyde and hydrocyanic acid as the raw material. Due to its toxicity, hydrocyanic acid must be handled carefully.
A method for producing optically active mandelic acid by microorganism-mediated asymmetric reduction of phenylglyoxylic acid having no substituent on the benzene ring, is known in the art (JP-A Sho 57-198096; JP-A Sho 57-198097; JP-A Sho 63-32492; JP-A Hei 6-7179, etc.).
Methods for obtaining optical active substances of mandelic acid derivatives that have substituents on the benzene ring through enzymatic reactions will be of great use. However, no enzymatic method practicable on an industrial scale is known in the art.